The index case or patient zero or proband is the initial patient in the population sample of an epidemiological investigation. Often scientists search for the index case to determine how the disease spread and what reservoir holds the disease in between outbreaks. Note that the index case is the first patient that indicates the existence of an outbreak. Earlier cases may be found and are labelled primary, secondary, tertiary, etc.

Patient zero is a somewhat less specific term than index case and is sometimes used to refer to the central patient in an epidemiological investigation rather than the first patient. When used in general to refer to such patients in epidemiological investigations, the term is not capitalized. When the term is used to refer to a specific person in place of that person's name within a report on a specific investigation, the term is capitalized as Patient Zero.

A Proband is the first affected family member who seeks medical attention for a genetic disorder.
Amongst the ancestors of the proband, there are other subjects with the manifest disease, but they might be unknown due to the lack of information regarding those individuals or the disease at the time they lived. Other ancestors might be undiagnosed due to the incomplete penetration or variable expression.The diagnostic of the proband raise the level of suspicion for the proband's relatives and some of them may be diagnosed with the same disease. Conventionally, when drawing a pedigree chart, instead of the first diagnosed person, the proband may be chosen between the manifestly ill ancestors (parents, grandparents) from the first generation where the disease is found.

In the early years of the AIDS epidemic, there was a lot of controversy about a so-called Patient Zero who was the basis of a complex transmission scenario compiled by Dr. William Darrow and colleagues at the Centers for Disease Control (CDC) in the US. This epidemiological study showed how 'Patient O' (for "Out of California" and mistakenly identified in the press as 'Patient Zero') had given HIV to multiple partners, who then in turn transmitted it to others and rapidly spread the virus to locations all over the world (Auerbach et al., 1984). In all, at least 40 of the 248 people diagnosed with AIDS by April 1982 were thought to have had sex either with him or with someone who had.